Personalized Treatment Modalities for Rectal Cancer: Advances in Neoadjuvant Treatment

Locally advanced rectal cancer treatment has shifted toward personalized, risk-adapted strategies that balance oncologic control with functional preservation while minimizing toxicity. A multidisciplinary team approach is essential, tailoring treatment guided by individual patient risk factors and priorities. Traditional neoadjuvant chemoradiation and subsequent total mesorectal excision has improved local control, but concerns remain regarding systemic failure and treatment-related morbidity. Total neoadjuvant therapy is now widely considered a preferred approach for more advanced tumors, enhancing systemic control, improving chemotherapy compliance, and facilitating organ preservation in select patients. Recent studies highlight that response-based treatment adaptation allows for better patient stratification, with selected patients who respond well to preoperative chemotherapy potentially omitting radiation without compromising outcomes and omitting surgery for patients with complete clinical responses to chemoradiation and chemotherapy. Advances in molecular profiling, particularly in mismatch repair deficiency or microsatellite instability-high tumors, have enabled the implementation of immune checkpoint inhibitors, permitting select patients to avoid both radiation and surgery, thereby reducing treatment-related toxicities. Future research should focus on validating predictive biomarkers, such as circulating tumor DNA, refining patient selection, and optimizing treatment monitoring while also developing novel therapeutic strategies to further personalize locally advanced rectal cancer management.